Gene tests for prostate cancer may be possible

“Scientists have isolated a set of 13 gene defects that can be used to identify men who are most at risk of developing life-threatening prostate cancer," The Independent reports.

Arguably the biggest challenge in treating prostate cancer is it’s unpredictable prognosis. In many men it is slow growing and causes no or very few symptoms. In other men it can be highly aggressive and quickly spread out of the prostate leading to fatal complications. Around 10,000 men die from prostate cancer each year in the UK.

In this new study, researchers hoped to determine how often certain genes are mutated in men with a strong family history of prostate cancer, and the subsequent risk of prostate cancer.

The researchers identified 13 different mutations in eight genes in 14 of the 191 men studied.

Men with one of these mutations had significantly increased odds of developing advanced prostate cancer. These valuable findings warrant further investigation.

So far they suggest that in men with a strong family history of prostate cancer, these particular genetic mutations are associated with a higher risk of advanced disease. It is likely to be some time before tests could be developed to reliably identify which men would be more likely to develop life-threatening prostate cancer and so target treatments.

Importantly, further studies would need to demonstrate that identifying men with these mutations actually saves lives, or alternatively spares men from unnecessary treatments.

Where did the story come from?

The study was carried out by researchers from The Institute of Cancer Research, London, in collaboration with researchers from The Royal Marsden NHS Foundation Trust, London and the University of Cambridge. It was funded by Prostate Cancer UK, The Institute of Cancer Research and The Everyman Campaign, The National Cancer Research Network UK, The National Cancer Research Institute, the National Institute for Health Research and Cancer Research UK.

The research was well described in the media, although one or two of the headlines may have led readers to think a genetic test for advanced prostate cancer was closer than it actually is.

What kind of research was this?

This was a cross-sectional study that aimed to determine how often certain genes are mutated in men with a strong family history of prostate cancer (these men had three or more cases of prostate cancer in their family, suggesting a strong predisposition to prostate cancer development).

The researchers looked at 22 tumour suppressor genes. Tumour suppressor genes function to ‘supress’ cancer development until they are inactivated by mutations. The researchers then aimed to estimate the risk of prostate cancer if these genes are mutated.

What did the research involve?

The researchers took blood samples from 191 men with familial prostate cancer (these men had three or more cases of prostate cancer in their family).

They extracted DNA from the blood samples, and looked at the sequence of 22 tumour suppressor genes.

The researchers then looked at the association between loss-of-function (LOF) mutations and clinical features of the disease, by comparing men with an LOF mutation with men who didn’t have an LOF mutation identified.

The researchers also performed a ‘segregation analysis’, a technique to determine whether there is evidence that LOF mutations increase the risk of prostate cancer.

What were the basic results?

Fourteen of the 191 men (7.3%) had an LOF mutation in one of the 22 tumour suppressor genes investigated. None of the men had more than one LOF mutation. The researchers identified 13 different LOF mutations in eight genes. The genes affected have roles in DNA damage and repair.

Men with LOF mutations were diagnosed at a similar age, had similar levels of prostate specific antigen (PSA) at diagnosis (a protein produced by the prostate), and had similar grades and stages of prostate cancer. However, men with LOF mutations were more likely to have cancer with lymph node involvement and metastasis (cancer that has spread); a more aggressive form of the disease.

If nodal involvement, spread to nearby organs (tumour stage 4, when the tumour has spread into other body organs nearby, such as the rectum [back passage], bladder, muscle or the sides of the pelvic cavity), or metastatic spread to other body organs were taken to characterise advanced disease, men with LOF mutations had increased odds of advanced disease (odds ratio [OR] 15.09, 95% confidence interval[CI] 2.95 to 95.81).

The researchers estimate that LOF mutations in any of the studied genes, confers a 94% increased risk of prostate cancer (relative risk [RR] 1.94, 95% CI 1.56 to 2.42).

How did the researchers interpret the results?

The researchers concluded that loss-of-function mutations (mutations that inactivate) in DNA repair pathway genes predispose people to familial prostate cancer and advanced disease. They go on to say that the clinical utility of these findings will become increasingly important as targeted screening and therapies become more widespread.

Conclusion

This study has identified 13 different loss of function mutations in eight genes present in 7.3% of the men with familial cancer studied.

Men with one of these mutations had significantly increased odds of advanced prostate cancer characterised by spread to the lymph nodes, to nearby organs (tumour stage T4), or metastatic spread to other organs of the body.

These valuable findings warrant further investigation. So far they suggest that in men with a strong family history of prostate cancer, these particular genetic mutations are associated with a higher risk of advanced disease. It is likely to be some time before a test could be developed which is able to tell reliably which men would be more likely to develop life-threatening prostate cancer and so target treatments.

The hope is that genetic screening could identify men at risk of prostate cancer in the same way as women can be currently screened for high risk breast cancer genes.

Of course, such aspirations need to be proven (or otherwise) in a real-world setting to see if genetic testing saved lives.